Coxsackievirus-A10 induced RIPK3-driven necroptosis to promote the formation of inflammatory response and enhance virus production via being recognized by TLR3

  • Mol Immunol. 2025 Feb:178:107-116. doi: 10.1016/j.molimm.2025.01.012.
Yajie Hu  1 ,  Xiaoli Deng  1 ,  Yaming Lv  1 ,  Chen Liu  1 ,  Juan Chen  1 ,  Jie Song  2 ,  Yunhui Zhang  3
Affiliations
  • 1. Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China.
  • 2. National & Local Engineering Center for Infectious Biological Products, Institute of Medical Biology, Chinese Academy of Medical Science and Peking Union Medical College, Kunming, China. Electronic address: [email protected].
  • 3. Department of Pulmonary and Critical Care Medicine, The First People's Hospital of Yunnan Province, China; The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan, China. Electronic address: [email protected].
PMID: 39889589 DOI: 10.1016/j.molimm.2025.01.012
Abstract

Neuronal death and neuroinflammation has been considered as the main contributors to the progression and deterioration of HFMD caused by CV-A10. Necroptosis is a lytic and inflammatory form of cell death that plays a crucial role in viral pathogenicity. Herein, our study showed that CV-A10-infected SH-SY5Y cells induced Necroptosis via activating RIPK3-depedent pathway, but not requiring RIPK1, and meanwhile triggered the release of inflammatory cytokines. Moreover, RIPK3-mediated Necroptosis was also involved in virus production, which did not require RIPK1 either. Finally, it was further verified that TLR3 drove RIPK3-mediated cell death by sensing CV-A10 RNA and activating RIPK3. Collectively, our study demonstrated that initiation of Necroptosis in SH-SY5Y cells induced by CV-A10 accelerated the formation of inflammatory response and promoted virus replication through triggering a TLR3-initiated RIPK3-dependent pathway of Necroptosis, which advanced the current understanding of Necroptosis for the neuropathogenesis of CV-A10 Infection.

Keywords
Coxsackievirus-A10 (CV-A10); Hand foot and mouth disease (HFMD); RIPK3-dependent necroptosis; Toll like receptor 3 (TLR3).
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